Advances in the Surgical Correction of Presbyopia
The development of inlays has long posed a challenge to the corneal physiologist—to preserve the nutrient flow through and/or around a potential barrier. Our understanding of corneal physiology has matured largely because of studies on tolerance of intrastromal prosthetic devices. In general, an intrastromal implant for the management of presbyopia should possess the following characteristics: thin, small diameter, high nutrient and fluid permeability, and should be implanted relatively deep in stroma depending on the intended mechanism of action.
Large, impermeable intrastromal inlays can impede metabolic, catabolic, and/or dehydration processes in the cornea. An adequate glucose supply from the aqueous humor anterior to the inlay is essential to prevent anterior stromal necrosis. Superficial implantation can also lead to unintended abrupt surface curvature changes and possible extrusion by mechanical means.
With the exception of intended depth of inlay placement, the surgical principles for implanting corneal inlays are similar among devices. Patients that are near dominant may prefer to have the inlay implanted in their distance dominant eye. Eye dominance should be assessed by both sensory and motor dominance assessment techniques. Ziemer Femto LDV (Ziemer Group AG, Port, Switzerland) offers pocket software and similar software is under development for IntraLase Femtosecond Laser (Abbott Medical Optics Inc., Santa Ana, CA). A keyhole-shaped plastic shield may also be placed in the cone of the patient interface to block pulses, resulting in a pocket instead of a flap (PS Binder et al, 2010; ARVO. Abstract 2868, unpublished). Improvements in femtosecond and nanosecond technology, such as increased repetition rates and tighter spot and line pulse separation, improve outcomes with smoother stromal beds, reduced forward light scatter, and possibly a less vigorous wound healing response (data on file, AcuFocus Inc., Irvine, CA).
Inalys may be placed in a stromal pocket or under a lamellar flap. The pocket technique provides a number of potential advantages. First, the majority of peripheral corneal nerves are preserved, which allows for maintained corneal sensitivity and potentially quicker visual recovery. Pocket procedures also preserve the peripheral biomechanical properties of the cornea, which like the anterior lamellae, provide a majority of the biomechanical corneal stability. Lastly, striae are not a concern as they can be with a lamellar flap. In contrast, creation of a lamellar flap can be an attractive alternative as it offers access to a stromal bed for excimer ablation, allowing for full control of the refractive target and the ability to treat ametropia. In addition, a lamellar flap allows easy access to the inlay in the event repositioning or removal is warranted. The primary difference in this technique from a traditional LASIK procedure is that the flap is replaced in a relatively dry manner so as to not displace the inlay from the estimated line of sight. Centration is critical for proper performance, and a few hundred microns can make a clinically significant difference. The basis for proper centration is using a coaxially fixated light source on a surgical microscope with patient-assisted fixation. A surgical marker is often useful to clearly identify the target position once it is established by taking into account the first Purkinje image and center of the entrance pupil as landmarks and accounting for the degree of angle [kappa]. New devices such as the AcuTarget (SMI, Berlin, Germany) are also in development to aid in identifying the proper inlay position.
Like all surgical procedures, less manipulation typically leads to quicker recovery and better outcomes. Placement depth will vary for each inlay design as each have different material properties and dimensions that must respect the physiology of the cornea. Depth of implantation plays a role in the corneal remodeling process and can affect inlay performance. Inlays designed to intentionally alter surface curvature tend to be implanted more superficially. Other inlays designs that utilize a different index of refraction or small aperture are typically implanted deeper to avoid surface curvature changes.
The KAMRA inlay by AcuFocus Inc. is a small aperture corneal inlay for treatment of presbyopia that is perhaps the furthest along in development and the regulatory process of the current generation of corneal inlays. The inlay utilizes the pinhole effect to increase depth of field by selecting for central light rays and minimizing refraction. The KAMRA is in the US Food and Drug Administration (FDA) trials for the treatment of near-plano presbyopia where inlays are implanted into a femtosecond laser enabled pocket at a depth of 200 μm. The KAMRA inlay is a 5-μm-thin biocompatible polyvinylidine fluoride disc. The 1.6-mm central annulus acts as a pinhole, and the outer diameter measures 3.8 mm. A slit-lamp photograph of the KAMRA inlay is shown in Figure 1. 8400 laser-etched openings of 5.5 to 11.5 μm maintain the metabolic flow to the anterior cornea and are distributed in a designed pseudorandom pattern to prevent diffraction issues at night. Examination and imaging of ocular structures are not affected by the inlay, and visual field testing of KAMRA subjects show thresholds remaining within preoperative values (data on file, AcuFocus Inc.). A combined LASIK and KARMA implantation procedure is gaining popularity outside the United States for the simultaneous treatment of ametropia and presbyopia, where the inlay is placed under a 200-μm LASIK flap after an excimer ablation. This procedure allows surgeons to set the postoperative refractive target, thereby optimizing a patient's refractive status and outcomes. Tomita has popularized a dual interface procedure, where pocket is created deeper to a previously made thin flap, either sequentially or from a pre-existing LASIK. This procedure combines the benefits of the pocket and flap techniques. Unlike other non–lens-based presbyopic treatments, including the inlays in development, the KAMRA continuously compensates for the progressive loss of accommodative amplitude by means of improvement in depth of focus with a small aperture. A contralateral comparison of the Optical Quality Analysis System (Visiometrics, Spain) demonstrates a broadened defocus curve and reduced simulated retinal blur in the implanted eye (Fig. 2). Future applications may include implantation in monofocal pseudophakic patients and postlaser vision correction patients who have become presbyopic.
(Enlarge Image)
Figure 1.
Postoperative slit-lamp photo of a KAMRA small aperture inlay. Courtesy of AcuFocus Inc.
(Enlarge Image)
Figure 2.
Contralateral comparison of the ocular quality assessment system after KAMRA small aperture inlay implantation in the right eye, demonstrates a broadened defocus curve as well as an improved point spread function and improved simulated retinal image at near. Courtesy of AcuFocus Inc.
Enrollment in the current FDA IDE clinical study has been completed, and clinical trials are underway to fulfill requirements for FDA approval. In an interim analysis, Waring IV reported monocular mean uncorrected near acuity (UCNA) of J3 at 1 month and J2 at 18 months compared with J8 preoperatively. Mean uncorrected intermediate visual acuity was 20/35 preoperatively and 20/26 at 18 months and mean uncorrected distance acuity (UCDA was 20/20 at 18 months. The KAMRA inlay is commercially available outside the United States. Seyeddain et al, reported 2-year data on the AcuFocus Inc. inlay implanted in 32 eyes and found that 96.9% of patients read J3 or better in the implanted eye with mean binocular UCNA improvement from J6 preoperatively to J1 after 24 months. Mean binocular uncorrected intermediate visual acuity was 20/20 at 1 month and remained 20/20 throughout 24-month follow-up and mean UCDA of 20/20 in the implanted eye and 20/16 binocularly. Yilmaz and colleagues reported 1-year data on 39 presbyopic patients; 12 were naturally emmetropic and 27 had emmetropia resulting from previous hyperopic laser in situ keratomileus. Of the 39 inlays implanted, 3 were explanted during the study. At 1 year, the mean uncorrected near visual acuity (UCNVA) improved from J6 (preoperatively) to J1+. All implanted eyes had an UCNA of J3 or better and 85.3%, of J1 or better. Binocularly, the mean UCNA remained J1 or better throughout the study. The mean uncorrected distance visual acuity (UCDVA) in eyes with an inlay did not change significantly from preoperatively and remained 20/20 throughout the study period. All 3 eyes with inlay explantation returned to within ±1.00 D of the preoperative refractive state for near and distance vision, with no loss of best corrected distance visual acuity (CDVA). Tomita and colleagues reported 6-month data on 128 eyes evaluating the safety and efficacy of bilateral LASIK with simultaneous implantation of a KAMRA inlay in the nondominant eye. The mean logMAR UCNA in the eye with the inlay improved 7 lines in hyperopic eyes, 6 lines in emmetropic eyes, and 2 lines in myopic eyes. The mean logMAR UCDA improved by 3 lines, 1 line, and 10 lines, respectively.
The Raindrop corneal inlay, formerly known as the Presbylens and then the Vue+ (ReVision Optics, Lake Forest, CA), was developed in 2007 for the treatment of plano presbyopia. The Raindrop is a permeable hydrogel lenticule, which allows for fluid and nutrient flow. Recent design changes have included an enlarged diameter from 1.5 to 2 mm, which expands the near optical zone, improving useful near vision. The lentiule is approximately 10 μm thick at the periphery and ranges from 24 to 40 μm thick at the center. The proprietary hydrogel-based material has a water content and refractive index similar to that of the human cornea. The inlay is inserted under either a LASIK flap or into a corneal pocket at a depth of approximately 120 to 130 μm in the nondominant eye. The lenticule improves near and intermediate by inducing a differential surface curvature change resulting in a multifocal cornea. Distance acuity is minimally affected as light rays paracentral to the 2-mm inlay remain primarily focused on the retina, particularly with a dilated pupil. Pupil constriction creates a pseudoaccommodative state, utilizing the steepened central cornea. A slit-lamp biomicroscopic photograph of the Raindrop is shown in Figure 3.
(Enlarge Image)
Figure 3.
Slit-lamp biomicroscopic photograph of the Vue+.
The Raindrop has received CE mark in the European Union and the US IDE is submitted and the company recently completed the first phase of US FDA clinical trials. Sharma and colleagues reported data on 8 near-plano presbyopic eyes with the 1.5-mm inlay placed under a microkeratome created lamellar flap. All eyes implanted retained 20/32 or better UCNA at 2 years postoperatively. The mean gain in UCNA was 3.6 lines with a binocular mesopic UCDA of 20/25 or better for all patients. All subjects reported that they were satisfied with the surgery and able to perform typical near tasks without glasses. In a concomitant animal study, the implanted eyes remained clear without any reaction to the corneal inlay. Slit-lamp examination at 1 year revealed clear corneas and histology data suggest that the inlay appeared to be inert (GD Sharma et al. 2010; ARVO Abstract 813, unpublished).
The Flexivue Microlens (Presbia, Amsterdam, the Netherlands) is the only corneal inlay in development utilizing refractive add power. The Microlens is composed of a hydrophilic acrylic polymer, measuring 3 mm in diameter with an edge thickness of 20 μm. This bifocal optical inlay has separate distance and near focal points. The central zone is free of refractive power, and the peripheral zone has a standard refractive power with an index of refraction higher than that of the cornea generating +1.25 to +3.00 D of add power. The Microlens is inserted into a stromal pocket with an insertion device into the nondominant eye concentric with the estimated line of sight.
The Flexivue Microlens has received the CE mark in Europe. Initial data from Europe and Latin America are promising, and clinical trials are underway to demonstrate safety and efficacy of this device. In a study of 43 patients (average age, 52 y) with a mean preoperative UCDA of 20/20 and mean UCNA of 20/50, all patients had an increase in the UCNVA after 1 week. By 1 year, 93% of patients had an UCNA of J2 or better.
The Icolens (Neoptics AG, Hunenburg, Switzerland) is the most recent corneal inlay in development. This hydrophilic acrylic hydrogel lens combines a neutral central zone with a peripheral optical zone of 3 D. This bifocal design delivers 2 images on the retina simultaneously, like a multifocal intraocular lenses (IOL). Distance vision is preserved with combined refractive effects of the pupil surrounding the lens and the central (neutral) zone of the lens. The peripheral positive refractive power of the lens provides near vision correction. This lens uses a proprietary inserter to deploy the inlay into a femtosecond enabled corneal pocket. At the time of this publication, data were not available for review.
Inlays for Presbyopia
Background
The development of inlays has long posed a challenge to the corneal physiologist—to preserve the nutrient flow through and/or around a potential barrier. Our understanding of corneal physiology has matured largely because of studies on tolerance of intrastromal prosthetic devices. In general, an intrastromal implant for the management of presbyopia should possess the following characteristics: thin, small diameter, high nutrient and fluid permeability, and should be implanted relatively deep in stroma depending on the intended mechanism of action.
Large, impermeable intrastromal inlays can impede metabolic, catabolic, and/or dehydration processes in the cornea. An adequate glucose supply from the aqueous humor anterior to the inlay is essential to prevent anterior stromal necrosis. Superficial implantation can also lead to unintended abrupt surface curvature changes and possible extrusion by mechanical means.
Surgical Technique and Theory
With the exception of intended depth of inlay placement, the surgical principles for implanting corneal inlays are similar among devices. Patients that are near dominant may prefer to have the inlay implanted in their distance dominant eye. Eye dominance should be assessed by both sensory and motor dominance assessment techniques. Ziemer Femto LDV (Ziemer Group AG, Port, Switzerland) offers pocket software and similar software is under development for IntraLase Femtosecond Laser (Abbott Medical Optics Inc., Santa Ana, CA). A keyhole-shaped plastic shield may also be placed in the cone of the patient interface to block pulses, resulting in a pocket instead of a flap (PS Binder et al, 2010; ARVO. Abstract 2868, unpublished). Improvements in femtosecond and nanosecond technology, such as increased repetition rates and tighter spot and line pulse separation, improve outcomes with smoother stromal beds, reduced forward light scatter, and possibly a less vigorous wound healing response (data on file, AcuFocus Inc., Irvine, CA).
Inalys may be placed in a stromal pocket or under a lamellar flap. The pocket technique provides a number of potential advantages. First, the majority of peripheral corneal nerves are preserved, which allows for maintained corneal sensitivity and potentially quicker visual recovery. Pocket procedures also preserve the peripheral biomechanical properties of the cornea, which like the anterior lamellae, provide a majority of the biomechanical corneal stability. Lastly, striae are not a concern as they can be with a lamellar flap. In contrast, creation of a lamellar flap can be an attractive alternative as it offers access to a stromal bed for excimer ablation, allowing for full control of the refractive target and the ability to treat ametropia. In addition, a lamellar flap allows easy access to the inlay in the event repositioning or removal is warranted. The primary difference in this technique from a traditional LASIK procedure is that the flap is replaced in a relatively dry manner so as to not displace the inlay from the estimated line of sight. Centration is critical for proper performance, and a few hundred microns can make a clinically significant difference. The basis for proper centration is using a coaxially fixated light source on a surgical microscope with patient-assisted fixation. A surgical marker is often useful to clearly identify the target position once it is established by taking into account the first Purkinje image and center of the entrance pupil as landmarks and accounting for the degree of angle [kappa]. New devices such as the AcuTarget (SMI, Berlin, Germany) are also in development to aid in identifying the proper inlay position.
Like all surgical procedures, less manipulation typically leads to quicker recovery and better outcomes. Placement depth will vary for each inlay design as each have different material properties and dimensions that must respect the physiology of the cornea. Depth of implantation plays a role in the corneal remodeling process and can affect inlay performance. Inlays designed to intentionally alter surface curvature tend to be implanted more superficially. Other inlays designs that utilize a different index of refraction or small aperture are typically implanted deeper to avoid surface curvature changes.
Small Aperture Inlay
The KAMRA inlay by AcuFocus Inc. is a small aperture corneal inlay for treatment of presbyopia that is perhaps the furthest along in development and the regulatory process of the current generation of corneal inlays. The inlay utilizes the pinhole effect to increase depth of field by selecting for central light rays and minimizing refraction. The KAMRA is in the US Food and Drug Administration (FDA) trials for the treatment of near-plano presbyopia where inlays are implanted into a femtosecond laser enabled pocket at a depth of 200 μm. The KAMRA inlay is a 5-μm-thin biocompatible polyvinylidine fluoride disc. The 1.6-mm central annulus acts as a pinhole, and the outer diameter measures 3.8 mm. A slit-lamp photograph of the KAMRA inlay is shown in Figure 1. 8400 laser-etched openings of 5.5 to 11.5 μm maintain the metabolic flow to the anterior cornea and are distributed in a designed pseudorandom pattern to prevent diffraction issues at night. Examination and imaging of ocular structures are not affected by the inlay, and visual field testing of KAMRA subjects show thresholds remaining within preoperative values (data on file, AcuFocus Inc.). A combined LASIK and KARMA implantation procedure is gaining popularity outside the United States for the simultaneous treatment of ametropia and presbyopia, where the inlay is placed under a 200-μm LASIK flap after an excimer ablation. This procedure allows surgeons to set the postoperative refractive target, thereby optimizing a patient's refractive status and outcomes. Tomita has popularized a dual interface procedure, where pocket is created deeper to a previously made thin flap, either sequentially or from a pre-existing LASIK. This procedure combines the benefits of the pocket and flap techniques. Unlike other non–lens-based presbyopic treatments, including the inlays in development, the KAMRA continuously compensates for the progressive loss of accommodative amplitude by means of improvement in depth of focus with a small aperture. A contralateral comparison of the Optical Quality Analysis System (Visiometrics, Spain) demonstrates a broadened defocus curve and reduced simulated retinal blur in the implanted eye (Fig. 2). Future applications may include implantation in monofocal pseudophakic patients and postlaser vision correction patients who have become presbyopic.
(Enlarge Image)
Figure 1.
Postoperative slit-lamp photo of a KAMRA small aperture inlay. Courtesy of AcuFocus Inc.
(Enlarge Image)
Figure 2.
Contralateral comparison of the ocular quality assessment system after KAMRA small aperture inlay implantation in the right eye, demonstrates a broadened defocus curve as well as an improved point spread function and improved simulated retinal image at near. Courtesy of AcuFocus Inc.
Regulatory Status and Results
Enrollment in the current FDA IDE clinical study has been completed, and clinical trials are underway to fulfill requirements for FDA approval. In an interim analysis, Waring IV reported monocular mean uncorrected near acuity (UCNA) of J3 at 1 month and J2 at 18 months compared with J8 preoperatively. Mean uncorrected intermediate visual acuity was 20/35 preoperatively and 20/26 at 18 months and mean uncorrected distance acuity (UCDA was 20/20 at 18 months. The KAMRA inlay is commercially available outside the United States. Seyeddain et al, reported 2-year data on the AcuFocus Inc. inlay implanted in 32 eyes and found that 96.9% of patients read J3 or better in the implanted eye with mean binocular UCNA improvement from J6 preoperatively to J1 after 24 months. Mean binocular uncorrected intermediate visual acuity was 20/20 at 1 month and remained 20/20 throughout 24-month follow-up and mean UCDA of 20/20 in the implanted eye and 20/16 binocularly. Yilmaz and colleagues reported 1-year data on 39 presbyopic patients; 12 were naturally emmetropic and 27 had emmetropia resulting from previous hyperopic laser in situ keratomileus. Of the 39 inlays implanted, 3 were explanted during the study. At 1 year, the mean uncorrected near visual acuity (UCNVA) improved from J6 (preoperatively) to J1+. All implanted eyes had an UCNA of J3 or better and 85.3%, of J1 or better. Binocularly, the mean UCNA remained J1 or better throughout the study. The mean uncorrected distance visual acuity (UCDVA) in eyes with an inlay did not change significantly from preoperatively and remained 20/20 throughout the study period. All 3 eyes with inlay explantation returned to within ±1.00 D of the preoperative refractive state for near and distance vision, with no loss of best corrected distance visual acuity (CDVA). Tomita and colleagues reported 6-month data on 128 eyes evaluating the safety and efficacy of bilateral LASIK with simultaneous implantation of a KAMRA inlay in the nondominant eye. The mean logMAR UCNA in the eye with the inlay improved 7 lines in hyperopic eyes, 6 lines in emmetropic eyes, and 2 lines in myopic eyes. The mean logMAR UCDA improved by 3 lines, 1 line, and 10 lines, respectively.
Space-occupying Inlay to Create a Hyperprolate Cornea
The Raindrop corneal inlay, formerly known as the Presbylens and then the Vue+ (ReVision Optics, Lake Forest, CA), was developed in 2007 for the treatment of plano presbyopia. The Raindrop is a permeable hydrogel lenticule, which allows for fluid and nutrient flow. Recent design changes have included an enlarged diameter from 1.5 to 2 mm, which expands the near optical zone, improving useful near vision. The lentiule is approximately 10 μm thick at the periphery and ranges from 24 to 40 μm thick at the center. The proprietary hydrogel-based material has a water content and refractive index similar to that of the human cornea. The inlay is inserted under either a LASIK flap or into a corneal pocket at a depth of approximately 120 to 130 μm in the nondominant eye. The lenticule improves near and intermediate by inducing a differential surface curvature change resulting in a multifocal cornea. Distance acuity is minimally affected as light rays paracentral to the 2-mm inlay remain primarily focused on the retina, particularly with a dilated pupil. Pupil constriction creates a pseudoaccommodative state, utilizing the steepened central cornea. A slit-lamp biomicroscopic photograph of the Raindrop is shown in Figure 3.
(Enlarge Image)
Figure 3.
Slit-lamp biomicroscopic photograph of the Vue+.
Regulatory Status and Results
The Raindrop has received CE mark in the European Union and the US IDE is submitted and the company recently completed the first phase of US FDA clinical trials. Sharma and colleagues reported data on 8 near-plano presbyopic eyes with the 1.5-mm inlay placed under a microkeratome created lamellar flap. All eyes implanted retained 20/32 or better UCNA at 2 years postoperatively. The mean gain in UCNA was 3.6 lines with a binocular mesopic UCDA of 20/25 or better for all patients. All subjects reported that they were satisfied with the surgery and able to perform typical near tasks without glasses. In a concomitant animal study, the implanted eyes remained clear without any reaction to the corneal inlay. Slit-lamp examination at 1 year revealed clear corneas and histology data suggest that the inlay appeared to be inert (GD Sharma et al. 2010; ARVO Abstract 813, unpublished).
Refractive Annular Add Lenticule
The Flexivue Microlens (Presbia, Amsterdam, the Netherlands) is the only corneal inlay in development utilizing refractive add power. The Microlens is composed of a hydrophilic acrylic polymer, measuring 3 mm in diameter with an edge thickness of 20 μm. This bifocal optical inlay has separate distance and near focal points. The central zone is free of refractive power, and the peripheral zone has a standard refractive power with an index of refraction higher than that of the cornea generating +1.25 to +3.00 D of add power. The Microlens is inserted into a stromal pocket with an insertion device into the nondominant eye concentric with the estimated line of sight.
Regulatory Status and Results
The Flexivue Microlens has received the CE mark in Europe. Initial data from Europe and Latin America are promising, and clinical trials are underway to demonstrate safety and efficacy of this device. In a study of 43 patients (average age, 52 y) with a mean preoperative UCDA of 20/20 and mean UCNA of 20/50, all patients had an increase in the UCNVA after 1 week. By 1 year, 93% of patients had an UCNA of J2 or better.
Multifocal Refractive Inlay
The Icolens (Neoptics AG, Hunenburg, Switzerland) is the most recent corneal inlay in development. This hydrophilic acrylic hydrogel lens combines a neutral central zone with a peripheral optical zone of 3 D. This bifocal design delivers 2 images on the retina simultaneously, like a multifocal intraocular lenses (IOL). Distance vision is preserved with combined refractive effects of the pupil surrounding the lens and the central (neutral) zone of the lens. The peripheral positive refractive power of the lens provides near vision correction. This lens uses a proprietary inserter to deploy the inlay into a femtosecond enabled corneal pocket. At the time of this publication, data were not available for review.